Stomatin modulates adipogenesis through ERK pathway and regulates fatty acid uptake and lipid droplet growth. Stomatin modulates adipogenesis through ERK pathway and regulates fatty acid uptake and lipid droplet growth

Controlling fatty acid uptake, lipid production and storage, and metabolism of lipid droplets (LDs), is closely related to lipid homeostasis, adipocyte hypertrophy and obesity. We report here that stomatin, a major constituent of lipid rafts, participates in adipogenesis and adipocyte maturation by modulating related signaling pathways. In adipocyte-like cells, increased stomatin promotes LD growth or enlargements by facilitating LD-LD fusion, as well as fatty acid uptake from extracellular environment by recruiting effector molecules, such as FAT/CD36 translocase, to lipid rafts to promote internalization of fatty acids. Stomatin transgenic mice fed with high-fat diets exhibit obesity, insulin resistance and hepatic impairments; however, such phenotypes are not seen if feeding the transgenic animals with regular diets. Inhibitions of stomatin by gene knockdown or OB-1 pharmacological treatments inhibit adipogenic differentiation and LD growth through downregulation of PPARγ pathway. Effects of stomatin on PPARγ involve ERK signaling; however, an alternate pathway may also exist. Differential expression analyses by microarray were performed comparing stomatin-knockdown and control 3T3-L1 adipocyte-like cells. Overall design: Gene modified 3T3-L1 were differentiated to day7 and harvested for RNA extraction and hybridization on Affymetrix microarrays.